Evidence-Based Checklist to Delay Cardiac Arrest in Brain-Dead Potential Organ Donors

This cluster randomized clinical trial evaluates the use of a clinical management checklist and incidence of cardiac arrest in brain-dead potential organ donors in Brazil.


Contraindications due to hemodynamic instability
Severe clinical instability with the expectation of imminent cardiac arrest 9 8

Other contraindications
Contraindication to donation by the State Transplant Center 8 1 Total number of patients not included (% in relation to screened) 119 (13.8%) 117 (12.9%) Note: Exclusion criteria were grouped by affinity (italics) for flowchart summary (figure 1 of the main document).The sum of each category is different from that presented in the flowchart because some screened patients met more than one exclusion criterion.
The flowchart provides the first criterion met by the patient according to the study protocol, following the order presented in the table.

eFigure 2. Description of the adherence measurement
The following combination of goals and immediate action were used to measure adherence to the checklist to each potential donor:   -

eMethods 2. Exploratory outcomes according to the statistical analysis plan Exploratory outcomes according to the statistical analysis plan
Proportion of potential donors with adequate respiratory parameters, defined as PaO2/FiO2 ratio ≥200.
In the absence of simultaneously measured PaO2 and FiO2, adequate respiration was defined as To present the characteristics of sites and potential donors as a function of adherence at the site level, allowing to assess comparability between groups (selection bias).
Adherence to each checklist item (at the brain-dead potential organ donor level)

Steering committee
To describe adherence to each item individually in order to provide greater transparency about adherence to each item of the checklist at the potential donor level.Adherence to the intervention per site

Steering committee
To describe adherence per site individually in order to provide greater transparency about adherence at the site level.Post hoc analysis for the primary outcome combining site and brain-dead potential organ donor adherence to the intervention

Steering committee
To check the consistency of adherence to the checklist at the potential donor level stratified by adherence at the site level in order to investigate potential confounders or the occurrence of reverse causality.

Characteristics of the brain-dead potential organ donors at baseline considering adherence
to the intervention at the potential organ donor level

Steering committee
To present the characteristics of sites and potential donors as a function of adherence at the potential organ donor, allowing to assess comparability between groups (selection bias).

Steering committee
To compare the sites with the highest and lowest adherence to the checklist, descriptively, using proxies for site quality based on study data (time from inclusion in the study to organ harvesting, and time from inclusion in the study to the primary outcome) and based on data recorded in 2016 in the Brazilian National Transplant System (donation and cardiac arrest rates), allowing to assess comparability between groups and to investigate selection bias and confounding bias.Post hoc analysis by proxy for site quality using a directed acyclic graph (DAG)

Steering committee
To check the consistency of adherence to the checklist using proxies for site quality based on the 2016 data from the Brazilian National Transplant System (donation and cardiac arrest rates) in order to investigate potential confounders or the occurrence of reverse causality.

Analysis Requested by
Reason/Objective Post hoc analysis adjusted for the characteristics of sites and brain-dead potential organ donors considering site adherence to the intervention and using a directed acyclic graph (DAG)

Independent statistical board
To check the consistency of adherence to the checklist at the site level, adjusting the primary outcome for potential confounders of effects.
Post hoc analysis adjusted for the characteristics of braindead potential organ donors considering their adherence to the intervention and using a directed acyclic graph (DAG)

Steering committee
To check the consistency of adherence to the checklist at the potential donor level, adjusting the primary outcome for potential confounders of effects.
Post hoc ancillary analysis of the primary outcome according to adherence to the intervention at the potential donor level by quintiles of adherence

Steering committee
To describe the primary outcome rate according to quintiles of adherence at the potential donor level in order to investigate a dose-response gradient.

Steering committee
To describe adherence at the potential donor level according to the order of inclusion in the study (every 10 inclusions).

Steering committee
To check the consistency of adherence to the checklist at the potential donor level, adjusting the primary outcome for potential confounders of effects related to the site's learning curve for using the checklist.

Steering committee
To check the consistency of secondary regarding adherence to the intervention.
Post hoc analysis of the secondary outcomes considering adherence to the intervention in the site level

Steering committee
To check the consistency of secondary regarding adherence to the intervention.

Descriptive analysis
blood pressure >90 mm Hg during the first clinical examination for brain death diagnosis 1 0

eFigure 1 .
Logic model for study development Adapted from study protocol: Westphal GA, Robinson CC, Biasi A, et al.DONORS (Donation Network to Optimise Organ Recovery Study): Study protocol to evaluate the implementation of an evidence-based checklist for brain-dead potential organ donor management in intensive care units, a cluster randomised trial.BMJ Open.2019;9(6):e028570.
with Immediate action when status = 'no' 9 10.Goal 9 combines with Immediate action when status = 'no' 10 11.Goal 10 combines with Immediate action when status = 'no' 11 12. Goal 11 combines with Immediate action when status = 'no' 12

□□□□--
Have all family members sitting down □ Leave land-line phones off the hook and turn off mobile phones □ Avoid crossing your arms or legs □ Have a trustful look and a serene expression Speak in a gentle voice □ Speak in a fine cadence, use pauses □ Tolerate periods of silence □ Give full attention to what family members say, "Listen more and talk less" Greet everyone and introduce yourself □ Refer to the patient by his/her name □ Find out what the family knows about the case □ Ask family members what they want to know □ Summarize previous clinical data □ Use simple language, avoid unnecessary technical jargon Make your message clear, keep it short □ Acknowledge emotions and negative reactions Avoid expressions like "do not cry", "keep calm", "I know how you feel" □ The ICU physician is responsible for communicating about the confirmation of brain death □ Communicate the confirmation of brain death to the family -Preferably use the word 'death' instead of the expression 'brain death'.(despite all efforts, unfortunately your loved one died...) □ DO NOT talk about donation □ Wait silently for the family's reactions and needs □ Review and confirm that the family understands that the patient is dead Ask the family if they have any questions IMPORTANT: "Proceed to STEP 3 only after making sure that the family understands the death" □ Make sure the family knows how to reach Evaluate the possibility of a rescue interview for donation after family conflicts have been resolved -Consider withdrawing therapeutic support "The physician is legally and ethically entitled to withdraw therapeutic support, including mechanical ventilation, and release the body to the family."¶ -Complete the "Death Certificate" PREPARING FOR THE FAMILY INTERVIEW GROUNDS: Establishing an aid relationship with family members Triad: Respect, Empathy, and Authenticity STEP 4 -PLANNING THE APPROACH ACCORDING TO THE FAMILY'S DECISION DEATH CERTIFICATE or FORENSIC MEDICAL EXAMINATION ICU physician's responsibility □ NON-VIOLENT DEATH -Complete the "Death Certificate" including the date and time of death and the data of the last examination performed (2 nd clinical examination) or neuro-imaging evidence.Complete the "Forensic Medical Examination Referral Form" including the date and time of death and the data of the last examination performed (2 nd clinical examination) or neuro-imaging evidence.
Steering committee Rate of actual donors per site eFigure 3. Geographic distribution of the included sites Source: Westphal GA, Robinson CC, Biasi A, et al.DONORS (Donation Network to Optimize Organ Recovery Study): Study protocol to evaluate the implementation of an evidence-based checklist for brain-dead potential organ donor management in intensive care units, a cluster randomized trial.BMJ Open.2019;9(6):e028570.

eTable 2. Family interview support guide based on the Spanish model of communication in critical situations PREPARING FOR THE FAMILY INTERVIEW GROUNDS: Establishing an aid relationship with family members Triad: Respect, Empathy, and Authenticity READ THE ACTIONS BELOW CAREFULLY BEFORE EACH STEP OF THE FAMILY INTERVIEW 1. Arranging the location of the interview
□ Well-ventilated place or room □ Restricted access (avoid interferences) □ Enough space and chairs for all participants □ No barriers between interviewer and interviewee (e.g., table, chairs, etc.) □ Facial tissues and water are available □ Phones are turned off 2. Defining the interview participants □ ICU physician □ Transplant co-ordinator and/or ICU nurse are present

eTable 4. Post hoc analysis considering adherence to the intervention according to the time of brain-dead potential donor inclusion
Abbreviations: HR, hazard ratio; CI, confidence interval; IQR, interquartile range, Time since first inclusion is defined as the time difference between potential inclusion and first inclusion per site; Inclusion order is defined as the order of inclusion of the potential donor per site.©2023 Westphal GA et al.JAMA Network OpeneFigure 4.

Subgroup analysis of the primary outcome (loss of brain-dead potential organ donors due to cardiac arrest) CI, confidence interval; ICU, intensive care unit; SAPS, Simplified Acute Physiology Score.
© 2023 Westphal GA et al.JAMA Network Open eTable 5.

Estimated number of brain death notifications in each ICU (≤29 vs. >29, according to the stratification variable)
© 2023 Westphal GA et al.JAMA Network Open eTable 6.

Sensitivity analysis of secondary outcomes regarding adherence considering potential organ donor adherence to the intervention
© 2023 Westphal GA et al.JAMA Network Open eTable 7.

Characteristics of the brain-dead potential organ donors at baseline considering adherence to the intervention at the potential organ donor level
Abbreviations: IQR, interquartile range; SOFA, Sequential Organ Failure Assessment; SAPS, Simplified Acute Physiology Score.aIdentified at the time of first clinical examination.©2023 Westphal GA et al.JAMA Network Open Intervention sites were grouped according to the global median adherence of the intervention sites.Abbreviations: ICU, intensive care unit; IQR, interquartile range; SAPS, Simplified Acute Physiology Score; SOFA, Sequential Organ Failure Assessment; Chronic respiratory disease is defined as restrictive, obstructive, or vascular disease severe enough to limit performance of the activities of daily living or chronic hypoxia, hypercapnia, polycythemia, pulmonary hypertension, or ventilator dependence; Chronic liver disease is defined as biopsy-proven cirrhosis or proven portal hypertension or previous history of hepatic insufficiency, encephalopathy, or coma.a Number of annual brain death notifications considers the percentage of brain-dead potential organ donors clinically managed in the intensive care unit.b Identified at the time of first clinical examination.eTable 9.

Post hoc analysis of secondary outcomes regarding adherence considering site adherence to the intervention
Abbreviations: RR, risk ratio; RD, risk difference; MD, mean difference; P.© 2023 Westphal GA et al.JAMA Network Open eTable 10.

Post hoc analysis for the primary outcome combining site and brain-dead potential organ donor adherence to the intervention
Abbreviations: CI, confidence interval; HR, hazard ratio.eFigure 5.

Correlation between adherence to the intervention per site and at individual level (potential donor adherence) eTable 14. Descriptive analysis for a proxy for site quality
Abbreviations: IQR, interquartile range.a Wilcox on test.